MR diffusion tensor imaging (DTI) is a promising technique for non-invasive mapping of neuronal connectivity in living human brain based on the directionality of water movement in white matter tracts. DTI is also a very useful technique for detecting abnormalities in white matter integrity, composition, and development caused by neuropsychiatric disorders. However, the potential of this technique to study complex and detailed cerebral connectivity is greatly limited by the low spatial resolution and poor signal-to-noise ratio of the single-shot technique that is currently in use. In this research proposal, new approaches to develop a robust high-resolution DTI technique with optimized signal-to-noise ratio will be studied. The proposed research in this application will resolve the technical shortcomings associated the single-shot method. These improvements are expected to improve significantly the robustness of DTI measurements. We plan to accomplish the objective of this application by pursuing three specific aims. Studies in specific aim one will develop a self-navigated multi-shot variable density spiral pulse sequence to acquire DTI data with sub-millimeter in-plane spatial resolution. Studies in specific aim two will combine the analysis of error propagation and numerical optimization into each step of DTI measurement to optimize the signal-to-noise ratio of DTI data by minimizing its noise sensitivity. Studies in specific aim three will conduct a pilot investigation of adolescents with disruptive behavior disorder using the optimized high-resolution DTI technique. Specifically, we will examine the correlation between abnormal anisotropy of white matter and measures of cognitive control. We expect that the optimized high-resolution DTI technique will have high sensitivity and specificity in identifying neuronal foci with abnormal diffusion anisotropy associated with a specific cognitive control malfunction. Collectively, the research proposed in this application will enhance our capability to map more detailed neuronal connectivity in the brain, which will advance our understanding of cognitive function and its disturbance in neuropsychiatric disorders.